The long-term objective of this proposal is to develop an effective phage-based antimicrobial therapy for the treatment of acne, targeting Propionibacterium acnes, the bacterium that contributes to the pathogenesis of the skin disease acne. We hypothesize that P. acnes bacteriophages, and/or their parts, can be identified as having a broad range of anti-P. acnes activity. Identification of the key biological features of these P. acnes bacteriophages will provide the necessary information to manipulate and modify the phage and its lysins for developing a highly specific acne therapy. The first goal will be to determine the diversity of P. acnes bacteriophages derived from skin of acne patients and normal donors in terms of the pattern of host range lysis and relevant genome differences. A novel aspect will be to develop a system for engineering P. acnes phage to optimize their host range and lytic activity. The second goal will be to elucidate the mechanisms by which bacteriophage lyse P. acnes, by cloning, expressing, purifying P. acnes lysine proteins, subsequently testing their biochemical activity and anti-bacterial activity against P. acnes clinical isolates. Together, these studies will provide new insight into the mechanisms by which bacteriophage derived from skin infect and lyse P. acnes information which can be leveraged towards developing a phage-based therapy for the treatment of acne. PUBLIC HEALTH RELEVANCE: The bacterium that contributes to the pathogenesis of acne can be attacked by viruses that live in human skin. We propose to learn about the mechanisms by which these viruses kill the acne bacteria in order to develop new therapies, to overcome the emergence of antibiotic resistant bacteria.